Efficacy of a Chinese herbal formula on hepatitis B e antigenpositive chronic hepatitis B patients

BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA viral load.AIM To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection.METHODS In total,395 patients(30–65 years old)with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk.Endpoints to evaluate therapeutic efficacy included:(1)HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96;and(2)HBeAg clearance and seroconversion rates at weeks 48 and 96.RESULTS HBV DNA levels≤4 log10 IU/mL were 10.05%at week 48 and 18.59%at week 96 in the treatment group.The HBeAg clearance and conversion rates were 8.54%and 8.04%at week 48 and 16.08%and 14.57%at week 96,respectively.However,HBV DNA levels≤4 log10 IU/mL were 2.55%and 2.55%at weeks 48 and 96,respectively,and the HBeAg clearance rates were 3.06%and 5.61%at weeks 48 and 96,respectively,in the control group.The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance.CONCLUSION High rates of HBV DNA reduction,HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase.The ability of the compound to modulate host immune function probably contributed to this effect.

Correlation of hepatitis B surface antigen expression with clinicopathological and biochemical parameters in liver biopsies: A comprehensive study

BACKGROUND Chronic viral B hepatitis(CHB)is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis.Currently,although combinations of different laboratory methods are used in the follow-up and treatment of CHB,the failure of these procedures in some cases has led to the necessity of developing new approaches.In CHB,the intrahepatic expression pattern of viral antigens,including hepatitis B surface antigen(HBsAg),is related to different phases of inflammation.However,many studies have focused on the intracytoplasmic properties of HBsAg staining,and HBsAg positivity in liver tissue has not been evaluated by objective quantitative methods.AIM To investigate the relationship of image analysis-based quantitative HBsAg expression and its staining patterns with clinicopathological factors and treatment in CHB.METHODS A total of 140 liver biopsies from treatment-naïve cases with CHB infection were included in this study.Following diagnosis,all patients were treated with entecavir(0.5 mg)and followed up at three-month intervals.The percentage of immunohistochemical HBsAg(p-HBsAg)expression in the liver was determined in whole tissue sections of biopsies from each case by image analysis.The immunohistochemical staining pattern was also evaluated separately according to 3 different previously defined classifications.RESULTS A positive correlation between p-HBsAg and serum levels of hepatitis B virus(HBV)DNA and HBsAg was observed(P<0.001).The p-HBsAg value was significantly higher in younger patients than in older patients.When the groups were categorized according to the hepatitis B e antigen(HBeAg)status in HBeAgpositive cases,p-HBsAg was correlated with HBV DNA,hepatitis activity index(HAI)and fibrosis scores(P<0.001).In this group,p-HBsAg and HBsAg expression patterns were also correlated with the viral response(VR)and the serological response(SR)(P<0.001).Multivariate analysis revealed that p-HBsAg was an independent predictor of either VR or SR(P<0.001).In HBeAg-negative patients,although HBsAg expression patterns were correlated with both HAI and fibrosis,no relationship was observed among p-HBsAg,clinicopathological factors and VR.CONCLUSION In pretreatment liver biopsies,the immunohistochemical determination of HBsAg expression by quantitative methods,beyond its distribution within the cell,may be a good predictor of the treatment response,especially in HBeAg-positive cases.

Soluble programmed death-1 is predictive of hepatitis B surface antigen loss in chronic hepatitis B patients after antiviral treatment

BACKGROUND Hepatitis B surface antigen(HBsAg)loss,a functional cure in patients with chronic hepatitis B(CHB)undergoing antiviral therapy,might be an ideal endpoint of antiviral treatment in clinical practice.The factors that contribute to the functional cure remain unclear,and the predictors of functional cure are worth exploring.The concentration and kinetics of soluble programmed death-1(sPD-1)in patients with CHB may play an important role in elucidating the immune response associated with functional cure after nucleos(t)ide analogs therapy.AIM To investigate the factors associated with HBsAg loss and explore the influence of sPD-1 Levels.METHODS This study analyzed the data and samples from patients with CHB who underwent antiviral treatment in a non-interventional observational study conducted at Peking University First Hospital in Beijing(between 2007 and 2019).All patients were followed up:Serum samples were collected every 3 mo during the first year of antiviral treatment and every 6 mo thereafter.Patients with positive hepatitis B e antigen levels at baseline and with available sequential samples who achieved HBsAg loss during antiviral treatment served as the case group.This case group(n=11)was further matched to 44 positive hepatitis B e anti patients without HBsAg loss as controls.The Spearman’s rank correlation test and receiver operating characteristic curves analysis were performed.RESULTS The sPD-1 Levels were higher in patients with HBsAg loss than in those without HBsAg loss from baseline to month 96,and the differences were significant between the groups at baseline(P=0.0136),months 6(P=0.0003),12(P<0.0001),24(P=0.0007),48(P<0.0001),and 96(P=0.0142).After 6 mo of antiviral treatment,the sPD-1 levels were positively correlated with alanine transaminase(ALT)levels(r=0.5103,P=0.0017),and the sPD-1 levels showed apparent correlation with ALT(r=0.6883,P=0.0192)and HBV DNA(r=0.5601,P=0.0703)levels in patients with HBsAg loss.After 12 mo of antiviral treatment,the sPD-1 levels also showed apparent correlation with ALT(r=0.8134,P=0.0042)and HBV DNA(r=0.6832,P=0.0205)levels in patients with HBsAg loss.The sPD-1 levels were negatively correlated with HBsAg levels in all patients after 12 mo of antiviral treatment,especially at 24(r=-0.356,P=0.0497)and 48(r=-0.4783,P=0.0037)mo.After 6 mo of antiviral treatment,the AUC of sPD-1 for HBsAg loss was 0.898(P=0.000),whereas that of HBsAg was 0.617(P=0.419).The cut-off value of sPD-1 was set at 2.34 log pg/mL;the sensitivity and specificity were 100%and 66.7%,respectively.CONCLUSION The sPD-1 levels at 6 mo can predict HBsAg loss after 144 mo of antiviral treatment.

Exploration of nucleos(t)ide analogs cessation in chronic hepatitis B patients with hepatitis B e antigen loss

BACKGROUND Nucleos(t)ide analogs(NAs)cessation in chronic hepatitis B(CHB)patients remains a matter of debate in clinical practice.Current guidelines recommend that patients with hepatitis B e antigen(HBeAg)seroconversion discontinue NAs after relatively long-term consolidation therapy.However,many patients fail to achieve HBeAg seroconversion after the long-term loss of HBeAg,even if hepatitis B surface antigen(HBsAg)loss occurs.It remains unclear whether NAs can be discontinued in this subset of patients.AIM To investigate the outcomes and factors associated with HBeAg-positive CHB patients with HBeAg loss(without hepatitis B e antibody)after cessation of NAs.METHODS We studied patients who discontinued NAs after achieving HBeAg loss.The Cox proportional hazards model was used to identify predictors for virological relapse after cessation of NAs.The cut-off value of the consolidation period was confirmed using receiver operating characteristic curves;we confirmed the cut-off value of HBsAg according to a previous study.The log-rank test was used to compare cumulative relapse rates among groups.We also studied patients with CHB who achieved HBeAg seroconversion and compared their cumulative relapse rates.Propensity score matching analysis(PSM)was used to balance baseline characteristics between the groups.RESULTS We included 83 patients with HBeAg loss.The mean age of these patients was 32.1±9.5 years,and the majority was male(67.5%).Thirty-eight patients relapsed,and the cumulative relapse rate at months 3,6,12,24,36,60,120,and 180 were 22.9%,36.1%,41.0%,43.5%,45.0%,45.0%,45.0%,and 52.8%,respectively.Twentysix(68.4%)patients relapsed in the first 3 mo after NAs cessation,and 35 patients(92.1%)relapsed in the first year after NAs cessation.Consolidation period(≥24 mo vs<24 mo)(HR 0.506,P=0.043)and HBsAg at cessation(≥100 IU/mL vs<100 IU/mL)(HR 14.869,P=0.008)were significant predictors in multivariate Cox regression.In the PSM cohort,which included 144 patients,there were lower cumulative relapse rates in patients with HBeAg seroconversion(P=0.036).CONCLUSION HBeAg-positive CHB patients with HBeAg loss may be able to discontinue NAs therapy after long-term consolidation,especially in patients with HBsAg at cessation<100 IU/mL.Careful monitoring,especially in the early stages after cessation,may ensure a favorable outcome.

Preparation of Sporozoite Antigen of E. tenella

[Objective] To provide antigen for preparation of monoclonal antibodies against E. tenella. [Method] Broiler chickens were inoculated with axenic culture of sporulated oocysts of E. tenella, and their feces were collected after 5 -10 d. After simple separation, the oocysts were spor- ulated, purified and counted to prepare sporozoite antigen. [ Result] This method used to prepare sporozoite antigen was simpler and easier than other methods. In addition, it required few specialized equipment and media, and it could be conducted in general laboratories. However, it needed long time. [ Condusion] The E. tenella oocysts have been isolated from chickens, and the sporozoite antigen with high protein concentration has been obtained.

Transformation of hepatitis B serologic markers in babies born to hepatitis B surface antigen positive mothers

AIM: To better understand the clinical significance of hepatitis B serologic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal serologic markers of hepatitis B via placenta and its transformation in these babies were investigated.METHODS: Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B serologic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers,HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24.CONCLUSION: HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxisprotected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.

Models for predicting hepatitis B e antigen seroconversion in response to interferon-α in chronic hepatitis B patients

AIM:To develop models to predict hepatitis B e antigen(HBe Ag)seroconversion in response to interferon(IFN)-αtreatment in chronic hepatitis B patients.METHODS:We enrolled 147 treatment-nave HBe Agpositive chronic hepatitis B patients in China and analyzed variables after initiating IFN-α1b treatment.Patients were tested for serum alanine aminotransferase(ALT),hepatitis B virus-DNA,hepatitis B surface antigen(HBs Ag),antibody to hepatitis B surface antigen,HBe Ag,antibody to hepatitis B e antigen(anti-HBe),and antibody to hepatitis B core antigen(anti-HBc)at baseline and 12 wk,24 wk,and 52 wk after initiating treatment.We performed univariate analysis to identify response predictors among the variables.Multivariate models to predict treatment response were constructed at baseline,12 wk,and 24 wk.RESULTS:At baseline,the 3 factors correlating most with HBe Ag seroconversion were serum ALT level>4×the upper limit of normal(ULN),HBe Ag≤500 S/CO,and anti-HBc>11.4 S/CO.At 12 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤250 S/CO,decline in HBe Ag>1 log10 S/CO,and anti-HBc>11.8 S/CO.At 24 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤5 S/CO,anti-HBc>11.4 S/CO,and decline in HBe Ag>2 log10 S/CO.Each variable was assigned a score of1,a score of 0 was given if patients did not have any of the 3 variables.The 3 factors most strongly correlating with HBe Ag seroconversion at each time point were used to build models to predict the outcome after IFN-αtreatment.When the score was 3,the response rates at the 3 time points were 57.7%,83.3%,and 84.0%,respectively.When the score was 0,the response rates were 2.9%,0.0%,and 2.1%,respectively.CONCLUSION:Models with good negative and positive predictive values were developed to calculate the probability of response to IFN-αtherapy.

Clinical utility of hepatitis B surface antigen kinetics in treatment-na?ve chronic hepatitis B patients during longterm entecavir therapy

AIM To investigate the utility of hepatitis B surface antigen(HBsAg) kinetics in chronic hepatitis B patients during long-term entecavir treatment.METHODS This retrospective study included treatment-na?ve chronic hepatitis B patients who received at least 2 years of consecutive entecavir treatment. Patients were followed up at three to six month intervals with liver biochemistry, hepatitis B virus DNA, and abdominal sonography. In hepatitis B e antigen(HBeAg)-positive patients, HBeAg levels were assessed every three to six month until results became negative. Serum HBsAg levels were determined at the baseline, oneyear and five-year time points. Liver cirrhosis was diagnosed through liver biopsy, imaging examinations, or clinical findings of portal hypertension. Hepatocellular carcinoma was diagnosed by histological examination or dynamic image studies.RESULTS A total of 211 patients were enrolled. The median treatment time was 5.24(2.00-9.62) years. Multivariate analysis showed that lower baseline HBsAg levels were associated with an earlier virological response, earlier hepatitis B e antigen(HBeAg) seroconversion, and earlier biochemical response in HBeAg-positive patients(cut-off value: 4 log IU/mL) and an earlier virological response in HBeAg-negative non-cirrhotic patients(cut-off value: 2.4 log IU/mL). Although HBsAg levels decreased slowly during long-term entecavir treatment, higher HBsAg decrease rates were found in the first year for HBeAg-positive non-cirrhotic patients, and patients with higher baseline HBsAg levels. More favorable clinical outcomes were not observed by a rapid HBsAg decline per se, but depended on lower baseline HBsAg levels.CONCLUSION Baseline HBsAg can be used to predict treatment responses. HBsAg levels and decrease rates should be considered together according to disease status while interpreting HBsAg changes.

High-dose hepatitis B immunoglobulin therapy in hepatocellular carcinoma with hepatitis B virus-DNA/hepatitis B e antigen-positive patients after living donor liver transplantation

AIM: To investigate the impact of high-dose hepatitis B immunoglobulin(HBIG) on hepatocellular carcinoma(HCC) and hepatitis B virus(HBV) recurrence and overall survival after living donor liver transplantation(LDLT).METHODS: We investigated 168 patients who underwent LDLT due to HCC, and who were HBV-DNA/hepatitis B e antigen(HBe Ag)-positive, from January 2008 to December 2013. After assessing whether the patients met the Milan criteria, they were assigned to the low-dose HBIG group and high-dose HBIG group. Using the propensity score 1:1 matching method, 38 and 18 pairs were defined as adhering to and not adhering to the Milan criteria. For each pair, HCC recurrence, HBV recurrence and overall survival were analyzed by the Kaplan-Meier method and the log rank test according to the HBIG dose. RESULTS: Among those who met the Milan criteria, the 6-mo, 1-year, and 3-year HCC recurrence-free survival rates were 88.9%, 83.2%, and 83.2% in the low-dose HBIG group and 97.2%, 97.2%, and 97.2% in the high-dose HBIG group, respectively(P = 0.042).In contrast, among those who did not meet the Milan criteria, HCC recurrence did not differ according to the HBIG dose(P = 0.937). Moreover, HBV recurrence and overall survival did not differ according to the HBIG dose among those who met(P = 0.317 and 0.190, respectively) and did not meet(P = 0.350 and 0.987, respectively) the Milan criteria. CONCLUSION: High-dose HBIG therapy can reduce HCC recurrence in HBV-DNA/HBe Ag-positive patients after LDLT.

Clinical significance of hepatitis B e antigen level measurement during long-term lamivudine therapy in chronic hepatitis B patients with e antigen positive

AIM: To determine the changes of quantitative hepatitis B e antigen (HBeAg) that predicts early detection of non- response or breakthrough to long-term lamivudine (LAM) therapy.METHODS: Among HBeAg positive chronic hepatitis B patients who failed to achieve HBeAg seroconversion within 12 mo, we retrospectively analyzed 220 patients who had received LAM more than 24 mo. RESULTS: The mean duration of LAM therapy was 36 (range, 24-72) mo. HBeAg seroconversion after the first 12 mo of LAM therapy was achieved in 53 (24.1%) patients. Viral breakthrough was observed in 105 (47.7%) patients. To find out whether the changing patterns of HBeAg levels can predict the outcome of LAM therapy, we analyzed the reduction rates of HBeAg levels during LAM therapy. Using the decrease more than 90% of pretreatment HBeAg levels, the sensitivity and specificity of response were 96.2% and 70.1%, respectively. Patients were divided into 3 groups according to the reduction patterns of the decrease of quantitative HBeAg: decrescendo, decrescendo-crescendo, no change or fluctuating groups. The optimal time to predict non- response or breakthrough was the first 9 mo of therapy. At 9 mo of therapy, 49 (92.5%) of 53 patients who had achieved HBeAg seroconversion were included in the decrescendo group. On the contrary, in the no change or fluctuating group, only four (7.5%) had achieved HBeAg seroconversion. Among patients who did not show the continuous decrease of HBeAg levels at 9 mo, 95.2% (negative predictive value) failed to achieve HBeAg seroconversion.CONCLUSION: Almost all patients who failed to showa continuous decrease of HBeAg levels at 9 mo of LAM therapy were non-response or breakthrough. Therefore, monitoring changes of HBeAg levels during LAM therapy in HBeAg positive chronic hepatitis B may be valuable for identifying patients who are at high risk of non-response or breakthrough.

Seroprevalence of hepatitis B surface antigen in pregnant women attending antenatal clinic in Honiara Solomon Islands,2015

AIM To determine the seroprevalence of hepatitis B surface antigen(HBsAg) among pregnant women attending antenatal clinic in Honiara, Solomon Islands. METHODS This descriptive cross-sectional study was carried out in seven area health centers in Honiara. From March to June 2015, identification of eligible pregnant women in each site was conducted using systematic random sampling technique. A total of 243 pregnant women who gave written informed consent were enrolled. Standardized tool was used to record demographics, obstetric history and serology results. HBsAg and hepatitis B e antigen(HBeAg) were tested using point-of-care rapid diagnostic test. All HBsAg positive samples were verified using enzyme-linked immunosorbent assay. RESULTS The mean age of participants was 26 ± 6 years. The overall hepatitis HBsAg prevalence was 13.8% with higher rate(22%) reported in women between 30-34 years of age. Majority of HBsAg positive participants were Melanesians(29 out for 33). None of the pregnant women in the 15-19 years and ≥ 40 years tested positive for HBsAg. There was no statistically significant difference in HBsAg prevalence by age, ethnicity, education and residential location. The overall HBeAg seroprevalence was 36.7%. Women between 20-24 years of age had the highest rate of 54.5%. Low level of knowledge about hepatitis B vaccination was reputed. Overall, 54.6% of participants were not aware of their hepatitis B vaccination status and only 65.2% of mothers reported their child had been vaccinated. CONCLUSION Hepatitis B is a disease of public health importance in Solomon Islands and emphasize the need for integrated preventative interventions for its control.

Human leukocyte antigen-DP loci are associated with the persistent infection of hepatitis B virus in Chinese population

A genome-wide association study recently showed that genetic variants in human leukocyte antigen (HLA)-DP loci were strongly associated with a risk of persistent infection of hepatitis B virus (HBV) in Japanese and Thai individuals and variants in interleukin 28B (IL-28B) have been associated with responses to anti-hepatitis C virus (HCV) treatment. The aim of this study was to investigate whether the HLA-DP loci and IL-28B were associated with different outcomes of chronic HBV infection (CHB) in Chinese subjects. The rs9277535 near HLA-DPB1,rs3077 near HLA-DPA1, and rs12979860 near IL-28B were genotyped by direct sequencing in 185 CHB patients and 193 self-limited hepatitis B virus (SLHBV)-infected subjects who recovered from HBV infection. The rs9277535 near HLA-DPB1 was strongly associated with CHB (P=0.000 018 1, OR=1.905). This association was observed independent of HBV e antigen (HBeAg) status and HBV viral loads in HBeAg-positive CHB patients (P=0.000 4, OR=1.956), in HBeAg-negative CHB patients (P=0.000 9, OR=1.857), and in HBeAg-negative CHB individuals without detectable levels of HBV DNA in serum (P=0.001 1, OR=2.05). The rs3077 near HLA-DPA1 was associated with CHB (P=0.020 6, OR=0.686 5) and HBeAg-positive CHB infection status (P=0.014 3, OR=0.604 7). Meanwhile, a genetic variation of insertion-deletion (INDEL) polymorphism (rs361527, -/ATAAATGTTGA) near HLA-DPA1 was found to be associated with CHB (P=0.030 7, OR=0.702 8) and HBeAg-positive CHB infection status (P=0.023 3, OR=0.619). However,the rs12979860 genotype near IL-28B had no correlation with CHB. This study demonstrated that in the Han Chinese populations, HLA-DP loci, but not IL-28B, were associated with persistence of infection in different outcomes of HBV-infected patients; however, the mechanism needs to be further investigated.

On-treatment quantitative hepatitis B e antigen predicted response to nucleos(t)ide analogues in chronic hepatitis B

AIM To investigate potential predictors for treatment response to nucleos(t)ide analogues(NAs) in hepatitis B e antigen(HBe Ag)-positive chronic hepatitis B(CHB) patients.METHODS Seventy-six HBeA g-positive CHB patients received 96-wkNAs optimized therapy(lamivudine and adefovir dipivoxil) were studied retrospectively. Serum hepatitis B surface antigen, HBeA g, hepatitis B core antibody, hepatitis B virus(HBV) DNA and alanine aminotransferase levels were quantitatively measured before and during the treatment at 12 and 24 wk. Stepwise logistic regression analyses were performed to identify predictors for treatment response, and areas under the receiver operating characteristic curves(AUROC) of the independent predictors were calculated.RESULTS Forty-three CHB patients(56.6%) achieved virological response(VR: HBV DNA ≤ 300 copies/mL) and 15 patients(19.7%) developed HBeA g seroconversion(SC) after the 96-wk NAs treatment. The HBe Ag level(OR = 0.45, P = 0.003) as well as its declined value(OR = 2.03, P = 0.024) at 24-wk independently predicted VR, with the AUROC of 0.788 and 0.736, respectively. The combination of HBe Ag titer < 1.3 lg PEIU/mL and its decreased value > 1.6 lg PEIU/mL at 24-wk predicted VR with a sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV) of 85%, 100%, 100% and 83%, respectively, and the AUROC increased to 0.923. The HBeA g level(OR = 0.37, P = 0.013) as well as its declined value(OR = 2.02, P = 0.012) at 24-wk also independently predicted HBeA g SC, with the AUROC of 0.828 and 0.814, respectively. The HBe Ag titer <-0.5 lg PEIU/mL combined with its declined value > 2.2 lg PEIU/mL at 24-wk predicted HBeA g SC with a sensitivity, specificity, PPV, NPV of 88%, 98%, 88% and 98%, respectively, and the AUROC reached 0.928.CONCLUSION The combination of HBeA g level and its declined value at 24-wk may be used as a reference parameter to optimize NAs therapy.

Practical approach in hepatitis b e antigen-negative individuals to identify treatment candidates

The natural history of chronic hepatitis B is characterized by different phases of infection,and patients may evolve from one phase to another or may revert to a previous phase.The hepatitis B e antigen(HBeAg)-negative form is the predominant infection worldwide,which consists of individuals with a range of viral replication and liver disease severity.Although alanine transaminase(ALT)remains the most accessible test available to clinicians for monitoring the liver disease status,further evaluations are required for some patients to assess if treatment is warranted.Guidance from practice guidelines together with thorough investigations and classifications of patients ensure recognition of who needs which level of care.This article aims to assist physicians in the assessment of HBeAgnegative individuals using liver biopsy or non-invasive tools such as hepatitis B s antigen quantification and transient elastography in addition to ALT and hepatitis B virus DNA,to identify who will remain stable,who will reactivate or at risk of disease progression hence will benefit from timely initiation of anti-viral therapy.

Significant histological changes are not rare in indeterminate‐phase chronic hepatitis B patients with hepatitis B e antigen‐negative and normal alanine aminotransferase levels

Background&Objectives:The degree of liver injury in indeterminate chronic hepatitis B(CHB)infection patients with Hepatitis B e antigen(HBeAg)‐negative and persistently normal alanine aminotransferase(PNALT)levels is yet unclear.Therefore,we aimed to assess liver histological changes in such patients by liver biopsy and explore possible predictors.Methods:Overall,711 HBeAg‐negative CHB patients with PNALT levels who underwent liver biopsy from January 2017 to June 2022 were included in this retrospective study.The relationships between histological changes and predictors were assessed by smooth curve fitting and multivariate logistic regression analysis models.Data were also analyzed using American Association for the Study of Liver Disease(AASLD)modified alanine aminotransferase(ALT)criteria.Results:The proportion of significant histological changes in the indeterminate phase was higher than that in the inactive phase(53.97%vs.41.33%).The adjusted odds ratios(aORs)of significant necroinflammation and histological changes for the indeterminate phase were 2.05 and 1.43,respectively,when compared with the inactive phase by multivariate logistic regression analyses.Significant histological changes in the‐phase were positively associated with age,ALT,Aspartate aminotransferase(AST),Hepatitis B surface antigen(HBsAg),and Hepatitis B virus(HBV)DNA levels but negatively correlated with platelet(PLT)levels.HBV DNA≥5 log10 U/L and PLT<200�109/L were independent predictive factors for assessing histological changes in indeterminate‐phase patients.Similar analysis findings were obtained using the two sets of modified ALT criteria.Conclusions:Significant histological changes are not rare in indeterminatephase CHB patients and are higher than in the inactive phase,regardless of the ALT criteria.Histological investigation is strongly suggested for intermediate stage patients with HBV DNA>5 log10 U/L or PLT<200�109/L and antiviral therapy should be considered for such patients.

六种常用血清学诊断模型对成人乙型肝炎e抗原阳性患者肝纤维化的诊断价值比较

目的比较六种常用血清学诊断模型对成人乙型肝炎e抗原阳性患者肝纤维化的诊断价值。方法选取山东省淄博市中心医院和中国人民解放军总医院第六医学中心2018年1月至2023年6月诊断为慢性乙型肝炎并行肝病理组织活检的265例患者为研究对象。采集临床常用的球蛋白与血小板比值(GPR)、纤维化4因子指数(FIB-4)、天冬氨酸转氨酶-血小板比率指数(APRI)、天冬氨酸转氨酶与丙氨酸转氨酶比值(AAR)、纤维化硬化指数(FCI)、S指数(S-index)六种血清学诊断模型的相关指标,以肝组织穿刺活检结果为“金标准”,应用受试者操作特征曲线评估六种模型的诊断效能。结果F1~F4期年龄、血小板计数、丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转肽酶、白蛋白、APRI、FIB-4、GPR、S-index和FCI比较,差异有统计学意义(P<0.05)。区分F_(1)~F_(4)时,GPR、APRI、FIB-4、FCI和S-index模型的曲线下面积均>0.70,AAR模型曲线下面积的95%CI为0.50。区分F_(1)与F_(2)~F_(4)、F_(1)~F_(2)与F_(3)~F_(4)、F_(1)~F_(3)与F_(4)时,GPR、APRI、FIB-4、FCI和S-index模型的曲线下面积均大于AAR模型(P<0.05)。结论FIB-4、GPR、S-index和FCI均能较好地区分乙型肝炎e抗原阳性慢性乙型肝炎患者肝纤维化的严重程度,APRI区分效能则按F_(1)~F_(4)的顺序呈逐渐降低趋势,AAR基本不能对肝纤维化的严重程度作出判断。

HBeAg诱导的免疫激活和免疫抑制在慢性乙型肝炎中的作用

HBV感染诱导的慢性乙型肝炎是导致肝硬化和肝癌的重要危险因素。半个世纪前,HBeAg在HBV感染者血清中首次被发现,尽管HBeAg并不参与HBV在肝细胞中的感染或复制,但其已被证实可干扰宿主先天性和适应性免疫反应,在慢性HBV感染的过程中发挥着重要的免疫激活和免疫抑制作用。HBV对于感染的肝细胞并没有细胞毒性,免疫应答介导的抗病毒作用和炎症反应决定HBV是否被清除或者诱导肝脏炎症相关疾病。因此,本文对HBeAg的形成及其在慢性HBV感染中引起的免疫激活和免疫抑制机制进行综述,重点论述HBeAg对先天免疫和适应性免疫细胞所引起的不同免疫效应,阐述了其诱导免疫反应的两面性,并探讨HBeAg在慢性HBV感染不同阶段间的转换作用。

血清E-cadherin、VEGF、CYFRA21-1水平在甲状腺癌患者手术前后的变化及其对术后复发转移的预测价值

目的探讨血清E-钙粘连蛋白(E-cadherin)、血管内皮生长因子(VEGF)、细胞角蛋白19片段抗原21-1(CYFRA21-1)水平在甲状腺癌患者手术前后的变化及其对术后复发转移的预测价值。方法选取118例行甲状腺癌根治术的分化型甲状腺癌(DTC)患者为研究组,118例健康体检者为对照组;根据术后6个月复发转移情况,将DTC患者分为复发转移组33例与未复发转移组85例。比较对照组与研究组(术前)、研究组手术前后、复发转移组与未复发转移组血清E-cadherin、VEGF、CYFRA21-1水平,采用ROC曲线分析上述各指标对术后复发转移的预测价值。结果研究组血清E-cadherin水平显著低于对照组,血清VEGF、CYFRA21-1水平显著高于对照组(P<0.05);研究组术后2周血清E-cadherin水平显著高于术前,血清VEGF、CYFRA21-1水平显著低于术前(P<0.05);未复发转移组术后2周血清E-cadherin水平显著高于术后复发转移组,血清VEGF、CYFRA21-1水平显著低于术后复发转移组(P<0.05)。术后2周上述各指标联合检测预测DTC患者术后复发转移的AUC为0.862,敏感度为90.91%,特异度为75.29%。结论DTC患者术后血清中E-cadherin表达上调,VEGF、CYFRA21-1表达下调,各指标联合检测对复发转移具有较高的预测效能,可作为临床评估DTC患者术后复发转移情况的辅助指标。

HPV感染相关CIN患者血清HLA-E和HLA-G表达与疾病进展及治疗后复发的相关性

目的探讨人乳头瘤病毒(HPV)感染相关宫颈上皮内瘤变(CIN)患者血清人类白细胞抗原E(HLA-E)、人类白细胞抗原G(HLA-G)表达及临床意义。方法选取2021年6~12月在河北中石油中心医院治疗的HPV感染相关CIN患者120例作为观察组,选取同期无HPV感染的CIN患者60例作为对照组,检测两组血清HLA-E和HLA-G表达水平,分析血清HLA-E和HLA-G表达与患者临床资料、治疗后复发的关系。结果观察组血清HLA-E和HLA-G水平分别为(75.59±18.28)pg/mL和(30.20±9.92)ng/mL,高于对照组,差异有统计学意义(P<0.05)。观察组CIN分级Ⅱ/Ⅲ级患者血清HLA-E和HLA-G分别为(83.33±13.90)pg/mL和(34.54±7.18)ng/mL,高于CIN分级Ⅰ级(P<0.05);观察组高危型HPV感染者血清HLA-E和HLA-G分别为(78.82±17.70)pg/mL和(32.23±9.43)ng/mL,高于低危型HPV感染者(P<0.05)。观察组血清HLA-E和HLA-G表达与CIN分级呈正相关(P<0.05)。复发患者治疗后1周血清HLA-E和HLA-G分别为(68.32±8.73)pg/mL和(24.43±5.58)ng/mL,高于未复发患者(P<0.05)。结论HPV感染相关CIN患者血清HLA-E和HLA-G表达与CIN分级呈正相关,同时与患者治疗后复发有一定关系。

Dynamic Characteristics of Serum Hepatitis B Surface Antigen in Chinese Chronic Hepatitis B Patients Receiving 7 Years of Entecavir Therapy

Background：The ultimate goal of hepatitis B treatment is hepatitis B surface antigen （HBsAg） seroclearance.Several factors have been suggested to be associated with the rate of HBsAg reduction in antiviral-naive or lamivudine therapy cohorts.However,there are few studies evaluating the factors during long-term entecavir （ETV） therapy.In the present study,we aimed to evaluate the factors to predict the outcome of ETV therapy for 7 years.Methods：A total of 47 chronic hepatitis B （CHB） patients treated with ETV monotherapy were included in this study.Liver biochemistry,hepatitis B virus （HBV） serological markers,serum HBV DNA,and HBsAg titers were tested at baseline,3 months,6 months,and yearly from 1 to 7.The associations between factors and HBsAg reduction were assessed using multivariate tests with repeated measure analysis of variance.Results：At baseline,serum HBsAg levels showed a positive correlation with baseline HBV DNA levels （r =0.625,P 〈 0.001）.The mean HBsAg titers after ETV treatment were significantly lower than the baseline titers （P ranges from 0.025 to 0.000,000,6）.The HBsAg reduction rate during the 1st year was greater compared to after 1 year of treatment （P 〈 0.05）.Multivariate test showed that hepatitis B e antigen （HBeAg） seroclearance and/or HBsAg reduction ≥0.5 log10 IU/ml at 6 months had a high negative predictive value （96.77%） for HBsAg seroclearance （P =0.002,P =0.012,respectively）.Conclusions：The HBsAg reduction rate during the 1st year was greater than that after 1 year of treatment.Further,HBeAg status and HBsAg levels at month 6 are the optimal factors for the early prediction of HBsAg seroclearance after long-term ETV therapy in CHB patients.